Evaluating the Safety and Pharmacokinetics of VRC-HIVMAB075-00-AB (VRC07-523LS) in the Sera and Mucosae of Healthy, HIV-Uninfected Adult Participants

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The purpose of this study is to evaluate the safety and pharmacokinetics of a human monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults.

Condition or disease

Intervention/treatment

Phase

HIV Infections

Biological: VRC07-523LS

Phase 1

Detailed Description:

This study will evaluate the safety and pharmacokinetics of a human monoclonal antibody (VRC07-523LS) in the sera and mucosae of healthy, HIV-uninfected adults.

Participants will be randomly assigned to one of two groups. Participants in Group 1 will receive 10 mg/kg of VRC07-523LS at Weeks 0, 16, and 32. Participants in Group 2 will receive 30 mg/kg of VRC07-523LS at Weeks 0, 16, and 32.

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Layout table for eligibility information

Ages Eligible for Study:

18 Years to 50 Years (Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

General and Demographic Criteria

Age of 18 to 50 years

Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study

Ability and willingness to provide informed consent

Assessment of understanding: volunteer demonstrates understanding of this study and completes a questionnaire prior to first study product administration with verbal demonstration of understanding of all questionnaire items answered incorrectly

Agrees not to enroll in another study of an investigational research agent until completion of the last required protocol clinic visit

Good general health as shown by medical history, physical exam, and screening laboratory tests

Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit. See the study protocol for US Low risk guidelines.

Laboratory Inclusion Values

Hemogram/Complete blood count (CBC)

Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were assigned female sex at birth, greater than or equal to 13.0 g/dL for volunteers who were assigned male sex at birth. For transgender participants who have been on hormone therapy for more than 6 consecutive months, determine hemoglobin eligibility based on the gender with which they identify (ie, a transgender female who has been on feminizing hormone therapy for more than 6 consecutive months should be assessed for eligibility using the hemoglobin parameters for persons assigned female sex at birth).

White blood cell (WBC) count equal to 2,500 to 12,000 cells/mm^3

WBC differential either within institutional normal range or with site physician approval

Platelets equal to 125,000 to 550,000/mm^3

Chemistry

Chemistry panel: Alanine aminotransferase (ALT) less than 1.25 times the institutional upper limit of normal and creatinine less than or equal to institutional upper limits of normal.

Virology

Negative HIV-1 and -2 blood test: US volunteers must have a negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA).

Reproductive status: A volunteer who was assigned female sex at birth must:

Agree to use effective contraception for sexual activity that could lead to pregnancy from at least 21 days prior to enrollment through the last required protocol clinic visit. Effective contraception is defined as using the following methods:

Condoms (male or female) with or without a spermicide,

Diaphragm or cervical cap with spermicide,

Intrauterine device (IUD),

Hormonal contraception, or

Any other contraceptive method approved by the HVTN 128 Protocol Safety Review Team (PSRT)

Successful vasectomy in any partner assigned male sex at birth (considered successful if a volunteer reports that a male partner has [1] documentation of azoospermia by microscopy, or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite sexual activity postvasectomy);

Tubal ligation

Or be sexually abstinent until at least 4 months following the last study product administration.

Volunteers who were assigned female sex at birth must also agree not to seek pregnancy through alternative methods, such as artificial insemination or in vitro fertilization until after the last required protocol clinic visit

Mucosal Specimen Collection

Volunteers 21 years of age and older who were assigned female sex at birth: Pap smear (verified by medical records) is required within:

the 3 years prior to enrollment with the latest result reported as normal or ASCUS (atypical squamous cells of undetermined significance), OR

the 5 years prior to enrollment, with the latest result reported as normal, or ASCUS with no evidence of high risk HPV.

If no Pap smear was done within the last 3 years (or within the last 5 years, if high risk HPV testing was performed), the volunteer must be willing to undergo a Pap smear with the result reported (verified by medical records) as normal or ASCUS prior to sample collection.

Willing to have mucosal secretions and tissue biopsies collected at several timepoints

Willing to abstain from sexual intercourse for the required period after each biopsy collection

Exclusion Criteria:

General

Weight greater than 115 kg

Blood products received within 120 days before first study product administration unless eligibility for earlier enrollment is determined by the HVTN 128 PSRT

Investigational research agents received within 30 days before first study product administration

Intent to participate in another study of an investigational research agent or any other study that requires non-HVTN HIV antibody testing during the planned duration of the study

Pregnant or breastfeeding

Vaccines and other Injections

HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 128 PSRT will determine eligibility on a case-by-case basis.

Immunosuppressive medications received within 30 days before first infusion (Not exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of oral/parenteral prednisone or equivalent at doses less than or equal to 20 mg/day and length of therapy less than 14 days)

Serious adverse reactions to VRC07-523LS formulation components (sucrose, histidine, and sorbitol; see study protocol for more information), including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.

Immunoglobulin received within 90 days before first infusion unless eligibility for earlier enrollment is determined by the HVTN 128 PSRT

Autoimmune disease (Not excluded from participation: Volunteer with mild, stable and uncomplicated autoimmune disease that does not require immunosuppressive medication and that, in the judgment of the site investigator, is likely not subject to exacerbation and likely not to complicate Solicited and Unsolicited AE assessments)

Immunodeficiency

Clinically significant medical conditions

Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:

A process that would affect the immune response,

A process that would require medication that affects the immune response,

Any contraindication to repeated infusions or blood draws, including inability to establish venous access,

A condition that requires active medical intervention or monitoring to avert grave danger to the volunteer's health or well-being during the study period,

A condition or process (eg, chronic urticaria or recent infusion with evidence of residual inflammation) for which signs or symptoms could be confused with reactions to the study product, or

Any condition specifically listed among the exclusion criteria below.

Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety, Solicited AEs, or a volunteer's ability to give informed consent

Psychiatric condition that precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years.

Current anti-tuberculosis (TB) therapy

Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report). Exclude a volunteer who:

If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined as consistently less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg diastolic. For these volunteers, blood pressure must be less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.

If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure greater than or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or equal to 100 mm Hg at enrollment.

Malignancy (Not excluded from participation: Volunteer who has had malignancy excised surgically and who, in the investigator's estimation, has a reasonable assurance of sustained cure, or who is unlikely to experience recurrence of malignancy during the period of the study)

Seizure disorder: History of seizure(s) within past three years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years

Asplenia: any condition resulting in the absence of a functional spleen

History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.

Mucosal Specimen Collection

A rectal condition (for rectal biopsies), such as an active infection or inflammation of the colorectal area (eg, an HSV-2 outbreak or inflamed hemorrhoids or colitis/diarrhea), internal hemorrhoids, or any other condition noted during screening rectal exam via anoscope or in medical history that in the opinion of the clinician represents a contraindication to mucosal sampling.

For those who were assigned female sex at birth (for vaginal and cervical biopsies), any condition noted during pelvic exam via speculum or in medical history that in the opinion of the clinician represents a contraindication to mucosal sampling (eg, bacterial vaginosis).

An active genital tract condition, such as an active infection or inflammation of the genital tract (eg, genital sores or ulcers, penile or abnormal vaginal discharge, genital warts that are symptomatic or requiring treatment) or any other condition that in the opinion of the clinician represents a contraindication to mucosal sampling.